title: Anti-ghrelin Spiegelmer inhibits exogenous ghrelin-induced increases in food intake, hoarding, and neural activation, but not food deprivation-induced increases.
abstract: Circulating concentrations of the stomach-derived "hunger-peptide" ghrelin increase in direct proportion to the time since the last meal. Exogenous ghrelin also increases food intake in rodents and humans, suggesting ghrelin may increase post-fast ingestive behaviors. Food intake after food deprivation is increased by laboratory rats and mice, but not by humans (despite dogma to the contrary) or by Siberian hamsters; instead, humans and Siberian hamsters increase food hoarding, suggesting the latter as a model of fasting-induced changes in human ingestive behavior. Exogenous ghrelin markedly increases food hoarding by ad libitum-fed Siberian hamsters similarly to that after food deprivation, indicating sufficiency. Here, we tested the necessity of ghrelin to increase food foraging, food hoarding, and food intake, and neural activation [c-Fos immunoreactivity (c-Fos-ir)] using anti-ghrelin Spiegelmer NOX-B11-2 (SPM), an l-oligonucleotide that specifically binds active ghrelin, inhibiting peptide-receptor interaction. SPM blocked exogenous ghrelin-induced increases in food hoarding the first 2 days after injection, and foraging and food intake at 1-2 h and 2-4 h, respectively, and inhibited hypothalamic c-Fos-ir. SPM given every 24 h across 48-h food deprivation inconsistently inhibited food hoarding after refeeding and c-Fos-ir, similarly to inabilities to do so in laboratory rats and mice. These results suggest that ghrelin may not be necessary for food deprivation-induced foraging and hoarding and neural activation. A possible compensatory response, however, may underlie these findings because SPM treatment led to marked increases in circulating ghrelin concentrations. Collectively, these results show that SPM can block exogenous ghrelin-induced ingestive behaviors, but the necessity of ghrelin for food deprivation-induced ingestive behaviors remains unclear.
authors.affiliation: Department of Biology and Obesity Reversal Center, Georgia State University, Atlanta, Georgia.
authors.forename: Brett J W
authors.initials: BJ
authors.lastname: Teubner
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bartness
mesh_terms: D000818:Animals; D001069:Appetite Regulation; D052157:Aptamers, Nucleotide / Q000008:administration & dosage / Q000378:metabolism*; D006224:Cricetinae; D004435:Eating; D005508:Food Deprivation; D054439:Ghrelin / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D060845:Hoarding; D007031:Hypothalamus / Q000378:metabolism*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D009474:Neurons / Q000378:metabolism*; D017111:Phodopus; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013997:Time Factors
chemical_list: D052157:Aptamers, Nucleotide; D054439:Ghrelin; C512263:NOX-B11-3; D016760:Proto-Oncogene Proteins c-fos
keywords: Siberian hamster; c-Fos; foraging; immunohistochemistry